APOE genotype is a major predictor of long-term progression of disability in MS

Background and objective: The authors recently reported that the APOE epsil on4 allele is associated with significantly greater progression of disabili ty in a 2-year follow-up of patients with MS. In this study, these findings are substantiated and extended in a much larger group of patients followed for up to 40 years. Methods: Two hundred five patients with clinically def inite MS who were genotyped for the APOE epsilon4 carrier state were includ ed. Groups of patients with (n = 41) and without (n = 164) APOE epsilon4 al leles were compared for latency to expanded disability status scale (EDSS) scores of 4.0 and 6.0 by Kaplan-Meier analysis with the log rank test. The results were adjusted for age at onset and sex by Cox regression analysis. Results: The APOE epsilon4 allele frequency in patients with MS (0.10) was similar to that in the general Israeli population. There was a significant effect of APOE genotype on the latency to reach EDSS 4.0 and 6.0 (p = 0.000 2 and p = 0.0006 by two-tailed log rank test). Median latencies were shorte r by 12 and 11 years in the APOE epsilon4 group for these outcomes. These r esults were significant after adjustment for age at onset and sex. Conclusi ons: The APOE epsilon4 allele is associated with significantly faster progr ession of disability in MS. This is the first genetic factor to be identifi ed with a major impact on the progression of disability in this disease.